1. Technical Field
The invention involves methods and materials related to making and using transgenic non-human animals with genomic disruptions affecting the expression of a transforming growth factor β-inducible early gene. The invention also relates to heart conditions and methods for treating heart conditions.
2. Background Information
TGFβ and members of its signaling pathway are tumor suppressors that regulate many diverse tissue and cell processes, including differentiation, apoptosis, and cell proliferation. For example, TGFβ inhibits proliferation, induces cell differentiation and apoptosis, and alters gene expression in different cell types. TGFβ-inducible early gene (TIEG) encodes a protein that is rapidly induced (as is its mRNA) by all three isoforms of TGFβ. TIEG protein is 480 amino acids in length (72 kDa) and contains a zinc finger region that has homology with the 3-zinc finger family of transcription factors (e.g., Sp-1, BTEB, EGR-1, and the Krüppel-like factors). The TIEG gene is localized on chromosome 8q22.2. TIEG protein has been identified in many human tissues and cell types, including cells in the breast, uterus, brain, pancreas, muscle, and bone. TIEG plays a role in TGFβ-induced inhibition of cell proliferation and apoptosis in human osteoblast cells, pancreatic carcinoma cells, and epithelial and liver cancer cells.